Sfrp5 serum concentration is associated with measures of glucose homeostasis and insulin sensitivity in human obesity

Background and aims: Secreted frizzled-related protein-5 (SFRP5) has been identified to antagonize Wnt signalling as a central pathway of adipogenesis which is related to metabolic disorders. Mice with a disruption of SFRP5 have elevated fasting glucose and insulin levels upon high fat and high-sucrose diet. SFRP5 expression in mature adipocytes correlates with increasing adiposity.

Materials and methods: We investigated SFRP5 serum concentration in a cross-sectional study of 213 individuals with a wide range of age, BMI, body fat mass, and measures of glucose metabolism and insulin sensitivity. In addition, circulating SFRP5 was measured in two weight loss intervention studies investigating the effect of a 800kcal energy restricted diet combined with an intensive exercise program (n=19), and before and one year after gastric sleeve or Roux-en-Y bypass operations (n=14).

Results: SFRP5 serum concentration significantly correlates with parameters of glucose homeostasis (fasting plasma glucose; r=0.2; p=0.006, HbA1c; r=0.22; p=0.002), proinsulin (r=0.29; p=0.035), hsCRP (r=0.14; p=0.046), and to creatinin (r=0.16, p=0.027). Patients with T2D had higher circulating SFRP5 (318±217ng/ml; n=100) than patients with normal glucose metabolism (289±265ng/ml; n=109; p=0.029). Serum SFRP5 did not significantly change in response to diet/exercise related moderate and significant weight loss after bariatric surgery (p=0.2).

Conclusion: SFRP5 serum concentration is significantly higher in patients with type 2 diabetes and significantly correlates with fasting plasma glucose, serum proinsulin and HbA1c. Our findings suggest a role for SFRP5 in the regulation of the glucose metabolism.